Effects of asymmetric dimethylarginine on renal arteries in portal hypertension and cirrhosis

作     者：Gloria Segarra Belén Cortina María Dolores Mauricio Susana Novella Paloma Lluch Javier Navarrete-Navarro Inmaculada Noguera Pascual Medina 

作者机构：Department of PhysiologyUniversity of Valencia and Institute of Health Research INCLIVAHospital Clínico Universitario Valencia Department of Gastroenterology and Hepatology and Institute of Health Research INCLIVAHospital Clínico Universitario Valencia 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2016年第22卷第48期

页      面：10545-10556页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：Supported by Consellería de Sanidad of the Generalitat Valenciana No.AP-052/08 

主　　题：Portal hypertension Cirrhosis Nitric oxide Asymmetric dimethylarginine Nitric oxide inhibitors Dimethylarginine dimethylaminohydrolase 

摘      要：AIM To evaluate the effects of asymmetric dimethylarginine(ADMA) in renal arteries from portal hypertensive and cirrhotic *** Rat renal arteries from Sham(n = 15), pre-hepatic portal hypertension(PPVL; n = 15) and bile duct ligation and excision-induced cirrhosis(BDL; n = 15) were precontracted with norepinephrine, and additional contractions were induced with ADMA(10-6-10-3 mol/L), an endogenous inhibitor of nitric oxide(NO) synthase. Concentration-response curves to acetylcholine(1 × 10-9^(-3) × 10^(-6) mol/L) were determined in precontractedrenal artery segments with norepinephrine in the absence and in the presence of ADMA. Kidneys were collected to determine the protein expression and activity of dimethylarginine dimethylaminohydrolase(DDAH), an enzyme that catabolizes ADMA. RESULTS In renal arteries precontracted with norepinephrine, ADMA caused endothelium-dependent contractions. The pD 2 values to ADMA were similar in the Sham and PPVL groups(4.20 ± 0.08 and 4.11 ± 0.09, P 0.05, respectively), but were lower than those of the BDL group(4.79 ± 0.16, P 0.05). Acetylcholine-induced endothelium-dependent relaxation that did not differ, in terms of p D2 and maximal relaxation, among the 3 groups studied. Treatment with ADMA(3 × 10^(-4) mol/L) inhibited acetylcholine-induced relaxation in the 3 groups, but the inhibition was higher(P 0.05) in the BDL group compared with that for the Sham and PPVL groups. The m RNA and protein expression of DDAH-1 were similar in kidneys from the three groups. Conversely, DDAH-2 expression was increased(P 0.05) in PPVL and further enhanced(P 0.05) in the BDL group. However, renal DDAH activity was significantly decreased in the BDL group. CONCLUSION Cirrhosis increased the inhibitory effect of ADMA on basal- and induced-release of NO in renal arteries, and decreased DDAH activity in the kidney.